Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco.
Department of Neurology, Columbia University, New York, New York.
JAMA Netw Open. 2024 Apr 1;7(4):e244266. doi: 10.1001/jamanetworkopen.2024.4266.
Frontotemporal lobar degeneration (FTLD) is relatively rare, behavioral and motor symptoms increase travel burden, and standard neuropsychological tests are not sensitive to early-stage disease. Remote smartphone-based cognitive assessments could mitigate these barriers to trial recruitment and success, but no such tools are validated for FTLD.
To evaluate the reliability and validity of smartphone-based cognitive measures for remote FTLD evaluations.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study conducted from January 10, 2019, to July 31, 2023, controls and participants with FTLD performed smartphone application (app)-based executive functioning tasks and an associative memory task 3 times over 2 weeks. Observational research participants were enrolled through 18 centers of a North American FTLD research consortium (ALLFTD) and were asked to complete the tests remotely using their own smartphones. Of 1163 eligible individuals (enrolled in parent studies), 360 were enrolled in the present study; 364 refused and 439 were excluded. Participants were divided into discovery (n = 258) and validation (n = 102) cohorts. Among 329 participants with data available on disease stage, 195 were asymptomatic or had preclinical FTLD (59.3%), 66 had prodromal FTLD (20.1%), and 68 had symptomatic FTLD (20.7%) with a range of clinical syndromes.
Participants completed standard in-clinic measures and remotely administered ALLFTD mobile app (app) smartphone tests.
Internal consistency, test-retest reliability, association of smartphone tests with criterion standard clinical measures, and diagnostic accuracy.
In the 360 participants (mean [SD] age, 54.0 [15.4] years; 209 [58.1%] women), smartphone tests showed moderate-to-excellent reliability (intraclass correlation coefficients, 0.77-0.95). Validity was supported by association of smartphones tests with disease severity (r range, 0.38-0.59), criterion-standard neuropsychological tests (r range, 0.40-0.66), and brain volume (standardized β range, 0.34-0.50). Smartphone tests accurately differentiated individuals with dementia from controls (area under the curve [AUC], 0.93 [95% CI, 0.90-0.96]) and were more sensitive to early symptoms (AUC, 0.82 [95% CI, 0.76-0.88]) than the Montreal Cognitive Assessment (AUC, 0.68 [95% CI, 0.59-0.78]) (z of comparison, -2.49 [95% CI, -0.19 to -0.02]; P = .01). Reliability and validity findings were highly similar in the discovery and validation cohorts. Preclinical participants who carried pathogenic variants performed significantly worse than noncarrier family controls on 3 app tasks (eg, 2-back β = -0.49 [95% CI, -0.72 to -0.25]; P < .001) but not a composite of traditional neuropsychological measures (β = -0.14 [95% CI, -0.42 to 0.14]; P = .32).
The findings of this cohort study suggest that smartphones could offer a feasible, reliable, valid, and scalable solution for remote evaluations of FTLD and may improve early detection. Smartphone assessments should be considered as a complementary approach to traditional in-person trial designs. Future research should validate these results in diverse populations and evaluate the utility of these tests for longitudinal monitoring.
额颞叶变性（FTLD）相对较少见，行为和运动症状增加了旅行负担，并且标准神经心理学测试对早期疾病不敏感。基于智能手机的远程认知评估可以减轻这些招募和成功的障碍，但没有针对 FTLD 的此类工具得到验证。
评估基于智能手机的认知测量在远程 FTLD 评估中的可靠性和有效性。
设计、设置和参与者：本队列研究于 2019 年 1 月 10 日至 2023 年 7 月 31 日进行，对照组和 FTLD 患者在 2 周内进行 3 次基于智能手机应用程序（app）的执行功能任务和联想记忆任务。通过北美 FTLD 研究联盟（ALLFTD）的 18 个中心招募观察性研究参与者，并要求他们使用自己的智能手机远程完成测试。在 1163 名符合条件的个体（参加母研究）中，有 360 名被纳入本研究；364 人拒绝，439 人被排除。参与者被分为发现（n=258）和验证（n=102）队列。在 329 名有疾病阶段数据的参与者中，195 名无症状或有临床前 FTLD（59.3%），66 名有前驱期 FTLD（20.1%），68 名有症状性 FTLD（20.7%），伴有一系列临床综合征。
参与者完成了标准的门诊测量和远程管理的 ALLFTD 移动应用程序（app）智能手机测试。
内部一致性、测试-重测可靠性、智能手机测试与标准临床测量的关联，以及诊断准确性。
在 360 名参与者（平均[标准差]年龄，54.0[15.4]岁；209[58.1%]名女性）中，智能手机测试显示出中等至良好的可靠性（组内相关系数，0.77-0.95）。有效性得到支持，因为智能手机测试与疾病严重程度（r 范围，0.38-0.59）、标准神经心理学测试（r 范围，0.40-0.66）和脑容量（标准化β范围，0.34-0.50）相关。智能手机测试可以准确地区分痴呆症患者和对照组（曲线下面积[AUC]，0.93[95%CI，0.90-0.96]），并且比蒙特利尔认知评估（AUC，0.68[95%CI，0.59-0.78]）更敏感（AUC，0.82[95%CI，0.76-0.88]）（比较的 z 值，-2.49[95%CI，-0.19 至-0.02]；P=0.01）。在发现和验证队列中，可靠性和有效性的发现非常相似。携带致病性变异的临床前参与者在 3 项应用程序任务上的表现明显差于非携带者家族对照（例如，2 回β= -0.49[95%CI，-0.72 至-0.25]；P<0.001），但不能综合传统神经心理学测量（β= -0.14[95%CI，-0.42 至 0.14]；P=0.32）。
这项队列研究的结果表明，智能手机可以为 FTLD 的远程评估提供一种可行、可靠、有效和可扩展的解决方案，并可能提高早期检测。智能手机评估应被视为传统亲身体验试验设计的补充方法。未来的研究应该在不同人群中验证这些结果，并评估这些测试在纵向监测中的效用。
